Citation

Abstract

The internists should utilize both their clinic experience and medical literature’s
evidences, mediating with organizational context, patients’ opinion and ethics. However,
none of these components may be sufficient.

In several medical sectors, we may find many and extensive grey zones in which a
diagnostic intervention’s effectiveness and/or its alternatives are uncertain.

This cannot lead to the decision-making process’s paralysis, because the evidencebased
medicine requires to base any clinical decision on “the best available evidences” and
not on “the best possible evidences.”

Clinicians should be able to extrapolate the prevailing question structuring from
patients’ problem (PICO: problem, intervention, confront, outcome); identify the best
available evidence and synthesize it; perform critical evaluation and information transfer
(critical appraisal); in clinical efficiency, evaluate any action options.

Keywords

Hospitalist; Internal Medicine; Clinical Error; Complexity

In general, medicine is considered as an inexact science for three
main reasons:

Failure rate and uncertainty are secondary to clinical error (being it
cognitive or system flaws-related: clinical risk)

Statistician William Deming showed how reduced is the acceptable failure rate in
several major business sectors “If we had to tolerate living with a level of efficiency equal
to 99.9 % we would have two dangerous landings a day, only in the O’Hare airport in
Chicago. Every hour there would be 16.000 failed correspondence addresses, and 32.000
bank cheques withdrawn from a wrong bank account.”

In comparison, medical practice exhibits a remarkable anomaly. If the error extent is
underestimated, the poor understanding of its nature is alarming as well.

In a recent study, physicians attributed the main failure rate to undersized staff
combined with work overload while they did not mention cognitive causes. However, several
studies show that the 1/6 of medical errors occurs synthetisizing available informations or
deciding to act according to these [1,2].

Failure rate is inherent in diagnostic process itself, which is highly
probabilistic

For example, for a proper diagnosis, diagnostic tests are not enough, because they
seldom give conclusive results. Tests sensibility and specificity are inherent characteristics,
which are usually provided by test manufacturers, or can be found in the literature. They
determine also [3]:

b. Biological variability of signs and symptoms’ occurrence: Vital signs (blood
pressure and heart rate) may vary on a daily basis and independently of other factors
(position, diet, stress, physical activity etc.) In addition, many measurements, including
those resulting from echocardiograms (for example, ejection fraction), are variable as well.

c. Cultural and scientific position: As to continuous measurements, such as sow
blood pressure, body mass, cholesterol or glucose tolerance, which cannot be expressed by
“positive-negative” dichotomy, the identification of a pathological threshold is arbitrary (as
it changes with new scientific data, industrial interests, economic sustainability).

d. Complex clinic judgment: Just as happens in any other field, even in the medical
area the same event can be interpreted in different ways, by different observers and at
different times.

Failure rate is related to lack of evidences and grey
zones presence

A recent perspective article published in theNew England Journal
of Medicine points out that one crucial issue may be the perception?
that health care is a twofold world in which interventions are either
effective or ineffective, appropriate or inappropriate. Actually, there
are large grey zones in which interventions are neither clearly
effective nor ineffective —where benefits are unknown or uncertain
and values may depend on patients’ preferences and available
alternatives.

Moreover, although in principle guidelines focus on
“appropriateness,” we should underline that appropriate care is not
the same as necessary care. Many areas of medicine have recently
undergone near continuous innovation process (imaging, cardiology,
oncology, and orthopedics), which involved a rapid cost growth.
Unfortunately, new tools “appropriate” use mostly occurs in grey
zones where, although a procedure is unlikely to be harmful, its
benefits may be modest or unproven [5].

As hospitalists, internists should utilize both their clinic
experience and medical literature’s “evidences”, mediating with
organizational context, patients’ opinion and ethics. However, none
of these components may be sufficient.

In several medical sectors, we may find many and extensive grey
zones in which a diagnostic intervention’s effectiveness and/or its
alternatives are uncertain.

This cannot lead to the decision-making process’s paralysis,
because the evidence-based medicine requires to base any clinical
decision on “the best available evidences” and not on “the best
possible evidences.”

Do we have necessary evidences for a therapeutic procedure?
Is the decision not to perform surgery secondary to cognitive bias
(diagnostic-therapeutic inertia/ omission bias)?

Clinical problem (PICO): In a patient with massive renal
synchronous neoplasia (RCC), is medical therapy, compared to
surgical therapy, the only way to improve survival?

Best available evidence identification: Nephrectomy is usually
recommended as a first step in RCC. However, since the observed
pathology (massive renal synchronous neoplasia) is unusual,
routinary recommendations cannot apply. Medline Literature’s
extensive research features only observational studies, retrospective
and international registers. It emerges that the extent of the disease
has no significant influence on the decision to perform surgery.
Patients with estimated survival time equal to < 12 mo or 4 further
IMDC (International Metastatic Renal Cell Carcinoma Database
Consortium) prognostic factors may not benefit from nephrectomy
whereas all other patients do [6-8].

Internist - Patient communication: After being informed on
risks (especially, the probable, imminent necessity for a dialysis
approach) and benefits (complete mass removal), the patient opted
for a radical surgery approach.

Evolution: Considering patient’s young age, good performance
status, medical history and will, the internist asked for a second
opinion in another Medical Center with a high number of relevant
clinical cases(as recommended in case of unusual diseases), where
the man underwent radical (right side) and partial (left side)
nephrectomy. One year later, he is still asymptomatic with good GFR.

Clinical case: In the last months, a 60-year-old woman has
experienced progressive asthenia, fever and paraplegia due to a
voluminous retroperitoneal, paravertebral mass which was difficult
to get access to, confirmed by abdominal tomography (TC).

We performed a guided TC biopsy (repeated twice because of
initially insufficient evidences) that showed a suspicious lymphoma
with two components:
-low kinetic phenotype index with germinal center.
-T-cells with high proliferative index/large cell B.

The slides were examined also in another reference center, where
they confirmed the apparent double population, although histological
report was lacking Negative osteomodullary biopsy.

Clinical problem (PICO): In a patient with a probable composite
lymphoma, has a histological characterization the greatest impact on
survival, even with diagnostic latency increase, or is a therapy tout
court more appropriate, considering the available histology?

Background: A composite lymphoma consists of two or more
different morphological types of malignant lymphoma affecting the
same organ or tissue. Most of the reported cases show a combination
of classic Hodgkin lymphoma with B-cell lymphoma. The cooccurence
of B and T cell lymphoma, however, is a rare event. Does
therapeutic latency, justified by hardly-obtained detailed diagnostics,
worsen the prognosis only?

Internist - patient communication: We talked to the patient
and his family, pointing out the difficulties her diagnosis involved, due
both to the mass ubication, and disease severity. We considered to
adopt a diagnostic surgical approach, although difficult to implement.
She asked to be moved to another Hematology department where she
started the therapy.

Evolution: The patient started the therapy for lymphoma B with
high proliferative index. The evolution was unfavourable. Even so,
following a meeting, a decision was taken by common agreement
between the internist, the hematologist colleagues, the patient and
her family. Unfortunately, the patient died 5 months later.

Clinical Case: Two years ago, a 55-year-old-man came
to our outpatient department with a chronic hepatitis B and
hepatic injury, which was interpreted as an angioma. His medical
history was negative, especially for alcohol/smoke abuse. Liver
tests were normal. He underwent US abdomen positive for
multiple liver hyperechoic nodules, attributed to hemangiomas,
but of uncertain nature, with abdomen CT/MRI performed
3 months before. FPDG PET was negative.

Clinical problem (PICO): In a patient with chronic hepatitis
B, should the presence of hepatic hyperechoic lesions be further
investigated for a better diagnostic outcome?

Background: Patients affected by rare diseases find it hard to
obtain good quality healthcare, due, among the others, to lack of
scientific and multidisciplinary healthcare knowledge as well as
to diagnostic delays. Cognitive bias accounts for late diagnosis and
ineffective therapeutic path, especially in the case of rare diseases
such as NET (neuroendocrine tumor), a long-unrecognized disease
(just like 90% of NET).

Internists’ role is to analytically reason on this diagnosis, and
introduce the patient to a multidisciplinary path.

Best available evidence identification: The guidelines suggest that
any injury in an unhealthy liver should be further investigated with
the highest possible level of evidence. The confounding bias here was
the exclusion of the most common pathologies, for the expectation
phenomenon (Ascertainment bias) [17-19].

However, according to the most recent NET guidelines, after
discussing with the patient and the NET Reference Centre, we
performed Ga68DOTANOC PET, positive for focal hypermetabolic
area in terminal ileum, mesenteric adenopathy, pericardic and
multiple liver nodules [18-19].

The patient started the therapy including Sandostatin LAR (1 for
every 28 days) and octreotide (0.1 x 2 for 7 days) and underwent ileal
resection and cholecystectomy.

After 3 months’ therapy he underwent radiometabolic therapy
and now, after one year, he is in good clinical conditions.

Clinical reasoning should allow for the inclusion of an unusual
pathology and should organize a multidisciplinary path.

Conclusion

Appropriateness is commonly understood as “the level
of assistance really necessary to the patient, for so it can become
appropriate to the best and newest available scientific evidences.”

Any “appropriate” decision complies with the six right things’
rule: the right medication, for the right individual, in the right
moment, from a right professional, in the right dose, with the right
documentation. Actions’ quality needs to be considered in relation
both to objectives and execution mode [20].

From the examined cases we clearly infer that medicine is a
complex system. The internists’ cultural background can be a helpful
guide in grey zones and beyond, by mediating six fundamental
points of view: the patient, the doctor, the evidences, the nonevidences,
the organizational/social/economic context and the inter
professional cooperation (Figure 1).